Biomedical subjects

F M Robertson

Publications and source records attributed to F M Robertson.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Interleukin-1alpha gene expression during wound healing.

Interleukin-1alpha is known to be constitutively produced by epidermal keratinocytes under normal conditions, and injection of this cytokine enhances wound reepithelialization. However, no studies have characterized the temporal sequence of interleukin-1alpha gene expression over the time course of wound healing, and the cellular sources of this cytokine have not been identified. In the present studies, levels of interleukin-1alpha messenger RNA in wound tissue isolated from SKH-1 hairless mice were characterized and the cells that produced interleukin-1alpha immunoreactive protein over a 10-day time course of wound healing were defined. A time-dependent upregulation in interleukin-1alpha gene expression occurred immediately (4 hours) after a full-thickness wound was made, which represented a four-fold increase over levels of cytokine gene expression detected in nonwounded skin. Upregulation of cytokine gene expression correlated with an immediate increase in plasma interleukin-1alpha levels and was followed by an increase in interleukin-1alpha immunoreactive protein localized to keratinocytes within the leading edge of the wound and epidermis, as well as to neutrophils within the dermis. The rapid increase in local and systemic interleukin-1alpha levels correlated with the infiltration of a significant number of neutrophils into the wound site and with the proliferation of both basal keratinocytes and dermal fibroblasts. Given the known ability of interleukin-1alpha to regulate proliferation and migration of epidermal keratinocytes and to indirectly induce leukocyte chemotaxis, the results of the present studies suggest that interleukin-1alpha may be an important cytokine with both local and systemic actions that are linked to the initiation of critical cellular events early in wound healing.

Journal Article↗

PubMedDate not supplied

Characterization of a murine model of acute lung injury (ALI): a prominent role for interleukin-1.

This report describes a model developed to study local and systemic events that occur as a result of acute lung injury (ALI). C57BL/6J mice were injected with a single intravenous dose (2, 4, and 6 micrograms) of 12-O-tetradecanoylphorbol-13-acetate (TPA). At 1, 2, 4, 12, 24, and 48 h, after injection, plasma was collected by sinus orbital puncture, bronchoalveolar lavage (BAL) was performed and cells and fluid were collected, lungs were perfused, and pulmonary tissue was isolated and processed for histological, immunochemical, and gene expression studies. The results indicate a dose-dependent increase in animal distress and a decrease in survival. TPA induced an early systemic response, reflected as an initial decrease in numbers of peripheral blood neutrophils at 1 h, followed at 2 h by a sustained increase. There was dose- and time-dependent increase in IL-1 beta mRNA synthesis, detected using RT-PCR, and in immunoreactive IL-1 alpha produced by both tissue-fixed pulmonary cells and cells within alveolar spaces. Infiltration of neutrophils into pulmonary tissue and increased protein content in BAL fluid was detected 2 h after injection of TPA. Disruptions in pulmonary architecture accompanied by the presence of highly vacuolated macrophages within the alveolar spaces and interstitial tissue were evident after IV injection of TPA. The study shows that injection of TPA induces reproducible dose- and time-dependent alterations in cell types, numbers, state of activation, and production of soluble mediators in the peripheral circulation within BAL and pulmonary tissue. Thus, this model offers a means to examine the cellular basis for the local and systemic alterations observed during ALI.

Animals↗

PubMedDate not supplied

Comparative chemopreventive activity of ibuprofen and N-(4-hydroxyphenyl) retinamide against the development and growth of rat mammary adenocarcinomas.

The chemopreventive effects of Ibuprofen on the development and growth of 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary tumors were examined. A well known breast cancer chemopreventive retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR) was also included in this study for comparison. At 7 days prior to receiving a single intragastric dose of 15 mg DMBA, rats were fed a control chow diet, as well as diets containing either 1000 mg/kg diet of Ibuprofen or 1.5 mmol/kg diet of 4-HPR. Ibuprofen and 4-HPR markedly increased tumor latency. At 112 days post DMBA intubation, tumor incidence was 86% in control rats as compared to 74% and 62% in rats receiving Ibuprofen, and 4-HPR diets respectively (p < 0.05). Ibuprofen and 4-HPR reduced tumor burden and tumor volume almost to the same extent. The control rats had an average of 2.26 tumors/rat compared to 1.42 and 1.46 tumors/rat in the Ibuprofen or 4-HPR groups respectively (p < 0.05). Similarly, average tumor volume was 3.25 cm3 in the control rats compared to 0.86 cm3 and 0.83 cm3 in rats receiving Ibuprofen and 4-HPR diets respectively (p < 0.05). These results suggest that Ibuprofen may have potential in the chemoprevention and treatment of breast cancer.

Adenocarcinoma↗

PubMedDate not supplied

Comparative ability of ibuprofen and N-(4-hydroxyphenyl)retinamide to inhibit development of rat mammary adenocarcinomas associated with differential inhibition of gene expression of cyclooxygenase isoforms.

A rodent model of carcinogen-induced mammary tumorigenesis was used to determine the comparative growth inhibitory effects of dietary administration of either 1000 mg/kg of the non-steroidal antiinflammatory drug (NSAID) ibuprofen or 1.5 mmol/kg of the synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR). In addition, the effects of these compounds on gene expression and protein production of the two isoforms of the cyclooxygenase (COX) gene which are responsible for prostaglandin production were examined. Experimental diets were provided to rats beginning at 7 days prior to administration of a single intragastric dose of 15 mg dimethylbenz[a]anthracene (DMBA) and diets were provided ad libitum until the study was terminated at 16 weeks later. Ibuprofen significantly decreased levels of gene expression of both COX-1 and COX-2 (p < 0.01). Although dietary 4-HPR did significantly diminish levels of COX-1 gene expression (p < 0.01) in rat mammary adenocarcinomas, this synthetic retinoid did not significantly inhibit COX-2 gene expression. COX-1 protein was localized to endothelial cells, infiltrating inflammatory cells, and tumor cells, while COX-2 protein was detected primarily within tumor cells. Although ibuprofen was more effective in inhibiting COX-2 gene expression than 4-HPR, ibuprofen and 4-HPR were equally effective in inhibiting development of carcinogen-induced mammary adenocarcinomas.

9,10-Dimethyl-1,2-benzanthracene↗